High vancomycin minimum inhibitory concentration is a predictor of mortality in meticillin-resistant Staphylococcus aureus bacteraemia

Failure of vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia has been reported despite full susceptibility of the organism to vancomycin. A retrospective observational cohort study including 137 patients with MRSA bacteraemia was performed at two centres in South Korea during 2009-2010. A total of 137 patients with MRSA bacteraemia receiving vancomycin therapy were enrolled during the study period. Isolates from 13 (9.5%) of the 137 patients had minimum inhibitory concentrations (MICs) ≥1 μg/mL. The 30-day cumulative survival was 53.8% for patients infected with isolates having a MIC≥1 μg/mL and 79.8% for patients infected with isolates having a MIC<1 μg/mL (log-rank test, P=0.026). Vancomycin MIC≥1 μg/mL [hazard ratio (HR)=7.0, 95% confidence interval (CI) 2.2-22.1; P=0.001], nosocomial acquisition of bacteraemia (HR=5.4, 95% CI 1.4-20.1; P=0.013), rapidly fatal underlying diseases (HR=20.5, 95% CI 3.9-106.4; P<0.001), presentation with septic shock (HR=8.4, 95% CI 3.0-23.3; P<0.001), presence of complicated infections (HR=5.6, 95% CI 2.0-15.8; P=0.001) and persistent MRSA bacteraemia for ≥3 days (HR=4.2, 95% CI 1.4-12.7; P=0.012) were independent predictors of 30-day mortality in patients with MRSA bacteraemia. In patients with high Pitt bacteraemia scores (Pitt score ≥2), the delay in initiation of vancomycin therapy was significantly different between non-survivors and survivors (2.4 days vs. 1.1 days; P=0.012). Vancomycin MIC≥1 μg/mL had a significant impact on mortality of patients with MRSA bacteraemia. These findings support early consideration of alternative anti-MRSA agents in patients with MRSA bacteraemia who have high vancomycin MICs as well as prompt initiation of anti-MRSA treatment in patients with MRSA bacteraemia, especially those with high Pitt scores.     

Risk factors influencing clinical outcome in Staphylococcus aureus bacteraemia in a Turkish University Hospital

A total of 101 episodes of Staphylococcus aureus bacteraemia were evaluated for the factors influencing prognosis. The overall episode mortality rate and the mortality rate due to bacteraemia were 43.6 and 21.8%, respectively. Episodes with methicillin-resistant S. aureus (MRSA) bacteraemia had a significantly higher overall mortality rate (58.7 vs. 30.9%, P<0.01) and mortality rate due to bacteraemia (32.6 vs. 12.7%, P=0.02) when compared with episodes caused by methicillin-sensitive S. aureus (MSSA). The multivariate analysis revealed that the underlying disease, presence of infective endocarditis, septic shock and central intravascular catheter and methicillin resistance of S. aureus were the five independent risk factors associated with a higher mortality rate.     

Multicentre study of risk factors for mortality in patients with Acinetobacter bacteraemia receiving colistin treatment

Colistin remains a last-line antibiotic for the treatment of infections by multidrug-resistant Acinetobacter species. However, mortality rates are high in patients with Acinetobacter infection receiving colistin treatment. This multicentre study evaluated whether colistin susceptibility, additional antimicrobial agents or other prognostic factors influenced the clinical outcomes of patients receiving colistin treatment for Acinetobacter bacteraemia. This retrospective study enrolled 122 adults receiving colistin for monomicrobial Acinetobacter bacteraemia at six medical centres in the ACTION Study Group over an 8-year period. Clinical information, antimicrobial susceptibility and colistin resistance determinants were analysed. The primary outcome measure was 14-day mortality. Among 122 patients, 18 and 104 were infected with colistin-resistant (ColR) isolates [minimum inhibitory concentration (MIC) ≥4 mg/L] and colistin-susceptible (ColS) isolates (MIC ≤2 mg/L), respectively. Patients infected with ColR and ColS isolates did not differ significantly with regard to Charlson comorbidity index, invasive procedures, sources of bacteraemia, disease severity and 14-day mortality rate (44.4% vs. 34.6%; P = 0.592). No specific additional antimicrobial agent was independently associated with higher or lower mortality. Coronary artery disease, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and bacteraemia caused Acinetobacter baumannii were independent risk factors associated with 14-day mortality. Mechanisms of colistin resistance were associated with amino acid variants in the pmrCAB operon. Finally, previously unreported Acinetobacter nosocomialis amino acid variants related to colistin resistance were identified. In conclusion, colistin susceptibility and colistin combination antimicrobial treatment were not associated with decreased 14-day mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.     

Outcome of patients with meticillin-resistant Staphylococcus aureus bacteraemia at an Emergency Department of a medical centre in Taiwan

The number of patients presenting to the Emergency Department (ED) with meticillin-resistant Staphylococcus aureus (MRSA) is increasing, but few studies focus on patients with bacteraemia. From January 2001 to June 2006 the clinical characteristics and outcome of 177 consecutive patients with MRSA bacteraemia visiting an ED of a university hospital were studied. The average age of the patients was 65.8 years. Healthcare-associated MRSA bacteraemia comprised 76.3% of all cases. Catheter-related bacteraemia was the most common type of infection (22.6%), followed by soft tissue infection (20.9%) and primary bacteraemia (15.3%). Different types of infection were significantly related to different outcome. In-hospital mortality was 33.3%, but the mortality decreased to 17.7% when patients with rapidly fatal disease and mortality within 3 days were excluded. All isolates exhibited lower susceptibility to vancomycin (minimum inhibitory concentration (MIC) 1-2mug/mL). Factors associated with mortality included severity of underlying illness, severity of bacteraemia and persistent bacteraemia. A detrimental effect of elevated MIC could not be demonstrated despite applying several definitions of patient outcome. Patients admitted to the ED with MRSA bacteraemia carry high overall mortality; however, the severity of underlying illness, severity of bacteraemia and persistent bacteraemia are correlated with mortality, but not vancomycin MICs (2mug/mL) of MRSA isolates.     

No effect of vancomycin MIC ≥ 1.5 mg/L on treatment outcome in methicillin-susceptible Staphylococcus aureus bacteraemia

The vancomycin minimum inhibitory concentration (MIC) has been shown to affect the outcome of methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. In this study, the outcomes of patients with MSSA bacteraemia with a vancomycin MIC?≥?1.5?mg/L were assessed. A prospective cohort of patients with MSSA bacteraemia in two tertiary-care hospitals was collected. The vancomycin MIC was determined by Etest. Staphylococcus aureus strains were categorised as low (<1.5?mg/L) or high (≥1.5?mg/L) vancomycin MIC. First- and second-line treatments were recorded and classified as optimal, appropriate and inappropriate. The primary endpoint was 30-day mortality. A total of 250 patients with S. aureus bacteraemia were analysed, of whom 64 (25.6%) had strains with a high vancomycin MIC. History of dialysis (P?=?0.001) and ultimately fatal disease (P?=?0.005) were associated with strains with a high vancomycin MIC. The 30-day mortality was 24.7% (46/186) in patients with a low vancomycin MIC versus 28.1% (18/64) in patients with a high vancomycin MIC (P?=?0.592) and did not differ significantly after adjustment for the appropriateness of the antibiotic treatment. Patients with a high vancomycin MIC were less frequently associated with complicated bacteraemia (15.6% vs. 39.2%; P?=?0.001). In conclusion, vancomycin MIC?≥?1.5?mg/L was not associated with 30-day mortality but was associated with uncomplicated bacteraemia in MSSA bacteraemia, regardless of the first- and second-line treatment.     

Association of rpoB mutations with rifampicin resistance in Mycobacterium avium

The susceptibility of clinical isolates of Mycobacterium avium to rifampicin (RIF) was examined. All 32 clinical isolates tested, including 18 from Japan, 13 from Poland and 1 from Thailand, were resistant to RIF (minimum inhibitory concentrations (MICs) > or =32 microg/mL for 17 isolates and 2-16 microg/mL for 15 isolates), whereas the type strain of M. avium ATCC 25291 was susceptible to RIF (MIC < or = 0.03 microg/mL). Mutations in nucleotides 1276-1356 of the rpoB gene, termed the 81 bp core region, are associated with RIF resistance in Mycobacterium tuberculosis. No mutations were found in this region in any of the M. avium clinical isolates tested. However, mutation of G-->A to give a Gly544-->Asp substitution was identified within the rpoB gene downstream of the 81 bp region in all clinical isolates. A RIF-resistant strain (ATCC 25291 Rif(r); MIC> or =32 microg/mL) obtained by culturing the type strain in RIF-containing broth possessed a mutation C-->T to give a His445-->Tyr substitution within the 81 bp region. When the rpoB gene of the ATCC 25291 Rif(r) strain and of a clinical isolate were inserted into Mycobacterium smegmatis, organisms with the ATCC 25291 Rif(r) sequence, but not those with the clinical isolate sequence, showed resistance to RIF. These results suggest that mutations of the 81 bp region of rpoB, as well as factors other than rpoB mutation, confer RIF resistance in M. avium.     

Topical antimicrobials in combination with admission screening and barrier precautions to control endemic methicillin-resistant Staphylococcus aureus in an Intensive Care Unit

We aimed to establish whether screening for methicillin-resistant Staphylococcus aureus (MRSA) and body decontamination upon admission to an Intensive Care Unit (ICU), in combination with barrier precautions, reduced rates of MRSA infection acquired on the unit. This was an interrupted time series study employing segmented regression analysis of data collected for all patients admitted to a 16-bed adult ICU over 48 months. Before the intervention (24 months; 1232 patients (44% female)), MRSA was sought from clinical cultures only and positive patients were barrier nursed in isolation. During the intervention (24 months; 1421 patients (54% female)), all ICU patients were screened for MRSA on admission and were barrier nursed in single rooms when established as MRSA-positive; all were given topical nasal anti-MRSA preparations and daily bed baths with 4% chlorhexidine throughout their stay. Changes in the proportion of patients colonised or infected with MRSA in the ICU were assessed. Before the intervention, 193 new MRSA cases (16%) were identified from 1232 ICU admissions; during the intervention, this was reduced to 92 cases (6%) of 1421 admissions. By time series regression analysis, the proportion of patients with MRSA decreased by 11.38% from ca. 15% to ca. 5% (ca. three-fold reduction) (95% confidence interval 3.5-19.3%; P=0.005). Thus, treatment of 11 patients prevented 1 clinical case of MRSA. Mean length of stay decreased significantly (P<0.001). Although MRSA and methicillin-susceptible S. aureus bacteraemia rates dropped, the changes detected were not statistically significant. The proportion of patients with coagulase-negative staphylococcal bacteraemia decreased significantly (P<0.001) and the trend changed from increasing to decreasing (P<0.001), as did the trend in glycopeptide use (P=0.014). An inexpensive and easy to implement intervention to control MRSA in the ICU was highly successful without compromising antimicrobial susceptibility.     

Antimicrobial susceptibility and staphylococcal chromosomal cassette mec type in community- and hospital-associated methicillin-resistant Staphylococcus aureus

STUDY OBJECTIVE: To differentiate the characteristics of community-associated methicillin-resistant Staphylococcus aureus (MRSA) and hospital-associated MRSA isolates on the basis of their susceptibility profiles, induction of clindamycin resistance, and staphylococcal chromosomal cassette (SCC) mec types. DESIGN: In vitro molecular and susceptibility study of isolates obtained from December 2004-January 2006 as part of a large, ongoing clinical study. SETTING: Level I trauma center in Detroit, Michigan. BACTERIAL STRAINS: Three hundred eight MRSA isolates randomly collected from patients; 130 were classified as community-associated, and 178 were classified hospital-associated by using definitions from the Centers for Disease Control and Prevention (CDC). INTERVENTION: Minimum inhibitory concentrations were tested on the basis of current guidelines from the Clinical and Laboratory Standards Institute. MEASUREMENTS AND MAIN RESULTS: All tested MRSA isolates were susceptible to daptomycin, linezolid, and vancomycin. In addition, community-associated MRSA isolates were significantly (all p < or = 0.05) more susceptible to trimethoprim-sulfamethoxazole (99%), clindamycin (96%), and a fluoroquinolone (76%) than hospital-associated MRSA isolates. Inducible resistance to clindamycin was demonstrated in 8.4% of community-associated MRSA isolates versus 50% of hospital-associated MRSA isolates (p < or = 0.001). Of interest, 35% of the MRSA isolates collected from hospitalized patients (> 48 hrs after admission and according to the CDC definition) possessed SCCmec type IV. CONCLUSION: Overall, inducible clindamycin resistance occurred at significantly higher rates in the hospital-associated MRSA isolates, susceptibility differed significantly between community- and hospital-associated MRSA, and most of the hospital isolates contained SCCmec type IV.     

Outcome of antibiotic therapy for third-generation cephalosporin-resistant Gram-negative bacteraemia: an analysis of 249 cases caused by Citrobacter,Enterobacter and Serratia species

Two hundred and forty-nine patients with monomicrobial bacteraemia due to third-generation cephalosporin (TGC)-resistant Citrobacter freundii (42), E. aerogenes (23), E. cloacae (143), and Serratia marcescens (41) were analyzed for antibiotic therapy used and outcome. For isolates with resistance to any of the TGCs, all beta-lactams, except imipenem, were considered ineffective. Of 152 patients given appropriate treatment, the mortality rates were 10.9% for 128 patients given monotherapy and 25.0% for 24 patients given combination therapy (P=0.09). Of patients given monotherapy, there were no significant differences in mortality between imipenem, aminoglycoside, and ciprofloxacin treatment groups (P=0.57). Only shock was associated with mortality in multivariate analysis. In conclusion, for patients with TGC-resistant Gram-negative bacteraemia, no significant difference in outcome was observed between single antibiotic therapy groups or monotherapy and combination therapy groups.     

MRSA bacteraemia

Methicillin-resistant Staphylococcus aureus (MRSA) has been pandemic for over a decade and is causing a major increase in serious staphylococcal infections. This is reflected in large increases in S. aureus bacteraemia with over 50% in many countries being caused by MRSA. Moreover, in some countries it also seems as though methicillin-susceptible S. aureus (MSSA) bacteraemia is also increasing. MRSA certainly has not replaced MSSA but is an additional burden with significantly higher mortality. Standard treatment of MRSA bacteraemia with glycopeptides is probably suboptimal in the presence of increasing resistance, MIC drift, uncertainties about laboratory susceptibility testing and fears of toxicity. New antibiotics look set to replace glycopeptides as the gold standard for treatment of MRSA bacteraemia, but whether the underlying causes of MRSA bacteraemia can be addressed successfully in order to control this pandemic disease is less certain.     

Standard treatment for Helicobacter pylori infection is suboptimal in non-ulcer dyspepsia compared with duodenal ulcer in Chinese

BACKGROUND: Recent studies suggest that the Helicobacter pylori eradication rate in patients with non-ulcer dyspepsia is lower when compared to patients with peptic ulcer diseases. AIM: The aim of this study was to study the efficacy of triple therapy for H. pylori infection in patients with duodenal ulcer vs. patients with non-ulcer dyspepsia. METHODS: A total of 582 Chinese patients with proven H. pylori infection were recruited to receive: omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg all given twice daily for 7 days (OCA regime). Endoscopy with rapid urease test, histology and culture were performed before treatment. Post-treatment H. pylori status was determined by (13)C-urea breath test. Metronidazole, clarithromycin and amoxicillin resistance was defined as minimum inhibitory concentration (MIC) of >8 microg/mL, >1 microg/mL and >1 microg/mL, respectively. RESULTS: A significantly higher (intention-to-treat/per-protocol) eradication rate was found in patients with duodenal ulcer than those with non-ulcer dyspepsia (91/94% vs. 84/88% respectively, P = 0.011 and P = 0.016). Clarithromycin resistance rate was higher in patients with non-ulcer dyspepsia than those with duodenal ulcer (14% vs. 6%, P = 0.015). Clarithromycin resistance (40% vs. 5%, P < 0.001, OR 12, 95% CI: 5.7-24.3) and the diagnosis of non-ulcer dyspepsia (91% vs. 84%, P = 0.011, OR 2.0, 95% CI: 1.2-3.3) significantly affected the success of H. pylori eradication. CONCLUSION: Clarithromycin resistance accounts for the significantly lower and suboptimal H. pylori eradication rate of OCA regimen in Chinese patients with non-ulcer dyspepsia compared to those with duodenal ulcer.     

Methicillin-resistant Staphylococcus aureus in the hospitals of central Greece.

A total of 250 consecutive Staphylococcus aureus clinical isolates were collected during the period 1999-2000 from the five major hospitals of the district of Thessaly (Central Greece). Thirty seven (14.8%) of the isolates were mecA-positive (MRSA) in a PCR-based assay; all exhibited resistance to oxacillin (agar dilution MICs > or =4 mg/L) and were also resistant to multiple antibiotics. Most of the MRSA isolates had been collected in the intensive care units and the surgical wards of the participating hospitals in a sporadic fashion. The MRSA incidence found here was significantly lower than reported in previous studies from Greece. Molecular typing by PFGE showed that the MRSA isolates were distributed between three pulsotypes. Evaluation of various conventional methods for assessing methicillin resistance showed that oxacillin agar dilution and immunological detection of PBP2a with the Slidex MRSA Detection kit were the most reliable in this setting. Misclassifications of isolates exhibiting low-level resistance (oxacillin MIC 2-4 mg/L) occurred with the salt agar screen, the oxacillin disk diffusion and the ATB Staph System methods.     

Pseudomonas aeruginosa bloodstream infections: how should we treat them?

Pseudomonas aeruginosa remains a major cause of bloodstream infections associated with high mortality. Adequacy of empirical therapy seems to influence outcome. Because of its high intrinsic resistance and its capacity to develop resistance during therapy, exposure to antimicrobial therapies frequently leads to subsequent P. aeruginosa bacteraemia with resistant isolates, increasing the risk of inadequate empirical therapy. Therefore empirical therapy should not include antimicrobial agents used in the last few months. Definitive combination therapy does not influence the prognosis of P. aeruginosa bacteraemia. Similarly, empirical combination therapy does not improve survival until receipt of the antibiogram. In contrast, empirical combination therapy does improve survival from the day of receipt of antibiogram to day 30. We therefore suggest that patients suspected of P. aeruginosa bacteraemia should receive empirical combination therapy until receipt of the antibiogram, followed by downgrading to an adequate monotherapy. This strategy might reduce mortality in P. aeruginosa bloodstream infections without exposing the patient to an excessive risk of adverse events. Antimicrobial therapies might select P. aeruginosa isolates with particular virulence phenotypes. The influence of specific virulence determinants on the prognosis of P. aeruginosa bacteraemia, as well as the potential benefit of virulence inhibition, deserves further investigation.     

Molecular epidemiology and mechanisms of rifampicin resistance in Acinetobacter baumannii isolates from Italy

Use of rifampicin (RIF) in combination with colistin (COL) has been proposed for the treatment of multidrug-resistant Acinetobacter baumannii infections owing to in vitro synergism. The aim of the present study was to evaluate the molecular epidemiology and mechanisms of RIF resistance in 57 clinical isolates of A. baumannii in two tertiary care hospitals in Naples (Italy) from 2006 to 2010. Amongst the collection, 36 isolates showed high RIF minimum inhibitory concentrations (MICs) (256 mg/L to ≥512 mg/L), 16 showed intermediate MICs (8-16 mg/L) and 5 had low MICs (4 mg/L). Of the 36 isolates with elevated RIF MICs, 35 were assigned to sequence type ST2 and 1 to ST78. Amongst the 57 isolates, 35 carried at least one mutation in rpoB, including H535L in 9 isolates and double mutations D525N and P544L in 7 isolates, whilst 22 showed no rpoB mutations. Treatment with the efflux pump inhibitor phenyl-arginine-β-naphthylamide (PAβN) of resistant isolates with no mutations in rpoB and different RIF MICs reduced the MIC by >10-fold and restored the synergism between RIF and COL in time-kill studies, whilst it had no effect on strains carrying rpoB mutations. In conclusion, the emergence of elevated RIF MICs in A. baumannii isolates from our geographical area was mostly caused by mutations in rpoB; low to intermediate RIF MICs were also caused by altered membrane permeability to the drug. The phenomenon was contributed by the selection of two prevalent clones both assigned to ST2 genotype. These data may have implications for the correct identification of cases with A. baumannii infection that would not benefit from addition of RIF to COL.     

Clinical impact of cefepime breakpoint in patients with carbapenem-resistant Klebsiella pneumoniae bacteraemia

The application of cefepime breakpoint for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteraemia has not been explored. Adult cases of monomicrobial bloodstream infection (BSI) caused by cefepime-susceptible [minimum inhibitory concentration (MIC) ≤8 mg/L] K. pneumoniae isolates with carbapenem resistance between 2010 and 2015 were reviewed. Patients treated with cefepime were compared with those treated by other active agents using a propensity score-matched analysis to assess therapeutic effectiveness. The primary endpoint was 30-day crude mortality. A total of 114 patients experienced cefepime-susceptible CRKP bacteraemia and 40 (35.1%) died during hospitalisation. A total of 33 patients (28.9%) received cefepime therapy. Fifteen patients (13.2%) had BSI due to carbapenemase-producing isolates, and 86.7% (13/15) of carbapenemase-producing isolates were classified as cefepime susceptible dose-dependent (SDD). In the multivariate logistic regression analysis, 30-day mortality was independently associated with the presence of a critical illness [adjusted odds ratio (aOR) = 12.89, 95% confidence interval (CI) 3.88–42.83; P < 0.001], pneumonia (aOR = 5.97, 95% CI 1.65–21.76; P = 0.007) and rapidly fatal underlying disease (aOR = 6.43, 95% CI 1.30–31.09; P = 0.02). In contrast, cefepime-based therapy (aOR = 0.03, 95% CI 0.003–0.38; P = 0.006) and combination therapy (aOR = 0.09, 95% CI 0.02–0.36; P = 0.001) were protective against a fatal outcome. Based on current breakpoints for Enterobacterales, cefepime therapy was not associated with an unfavourable outcome for CRKP BSI with MIC-based dosing strategies. However, the susceptibility result of SDD to cefepime should alert clinicians for possible therapeutic failure.     

利奈唑胺治疗耐甲氧西林金黄色葡萄球菌肺炎的疗效和影响因素分析

目的评价利奈唑胺治疗耐甲氧西林金黄色葡萄球菌肺炎的疗效,分析与疗效相关的影响因素。方法将2009年1月至2013年1月在我院接受利奈唑胺治疗的47例耐甲氧西林金黄色葡萄球菌肺炎患者根据疗效分为治疗有效组和治疗失败组。比较两组患者的性别、年龄、体重、炎症指标、APACHEⅡ评分、动脉血氧分压和基础疾病,进而通过二元逻辑回归分析找出影响疗效的因素。结果利奈唑胺的临床总有效率为72.3%。治疗失败组的PCT值和APACHEⅡ评分更高[分别为(1.38±0.67)mg/L对(0.91±0.32)mg/L,14.3±5.7对9.8±4.1,P=0.029和0.004),动脉血氧分压更低[(66±10)mmHg对(72±8)mmHg,P=0.016]。PCT值、APACHEⅡ评分和脑血管病是影响利奈唑胺治疗耐甲氧西林金黄色葡萄球菌肺炎疗效的临床因素。PCT的OR值为2.02(P=0.034,95%CI 1.06³.88),APACHEⅡ的OR值为1.41(P=0.013,95%CI 1.173.88),APACHEⅡ的OR值为1.41(P=0.013,95%CI 1.17¹.85),脑血管病的OR值为5.42(P=0.017,95%CI 1.691.85),脑血管病的OR值为5.42(P=0.017,95%CI 1.69⁴2.4)。结论利奈唑胺治疗耐甲氧西林金黄色葡萄肺炎的疗效良好,而高PCT值、高APACHEⅡ评分和脑血管病是治疗失败的主要危险因素。     

Nosocomial infections due to methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci at a university hospital in Taiwan from 1991 to 2003: resistance trends, antibiotic usage and in vitro activities of newer antimicrobial agents

A rapid increase of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection (from 39% in 1991 to 75% in 2003) and vancomycin-resistant enterococci (VRE) (from 1.2% in 1996 to 6.1% in 2003) at a university hospital in Taiwan was found. The noticeable rise of MRSA and VRE was significantly correlated with the increased consumption of glycopeptides, beta-lactam-beta-lactamase inhibitor combinations, extended-spectrum cephalosporins, carbapenems and fluoroquinolones (Pearson's correlation coefficient, P < 0.05). Minimum inhibitory concentrations (MICs) of 100 non-duplicate blood isolates of MRSA (in 2003) and of 25 non-duplicate isolates of vancomycin-resistant Enterococcus faecalis and 172 vancomycin-resistant Enterococcus faecium (in 1996-2003) causing nosocomial infection recovered from various clinical specimens of patients treated at the hospital to nine antimicrobial agents were determined by the agar dilution method. All of these isolates were susceptible to linezolid and were inhibited by 0.5mg/L of tigecycline, and all MRSA isolates were inhibited by daptomycin 1mg/L, including two isolates of MRSA with heteroresistance to vancomycin. Daptomycin had two-fold better activity against vancomycin-resistant E. faecalis (MIC90, 2 mg/L) than against vancomycin-resistant E. faecium (MIC90, 4 mg/L). Decreased susceptibilities of vancomycin-resistant E. faecium and MRSA to quinupristin/dalfopristin (non-susceptibility 25% and 8%, respectively) were found. Telithromycin had poor activity against the isolates tested (MIC90, 8 mg/L). Linezolid, daptomycin and tigecycline may represent therapeutic options for infections caused by these resistant Gram-positive organisms.     

Exposure to quinolones is associated with carbapenem resistance among colistin-susceptible Acinetobacter baumannii blood isolates

In this study, we explored risk factors associated with bacteraemia caused by colistin-susceptible/carbapenem-resistant (Co(S)/Ca(R)) Acinetobacter baumannii. A retrospective cohort study of hospitalised patients with A. baumannii bacteraemia was performed at a tertiary care hospital over a 44-month period. Thirty-nine patients with bacteraemia due to A. baumannii (35 Intensive Care Unit and 4 ward patients) were included in the analysis. Twenty-five patients (64%) had bacteraemia due to Co(S)/Ca(R)A. baumannii and 14 patients (36%) had bacteraemia due to colistin-susceptible/carbapenem-susceptible A. baumannii. Mortality was 56% (14/25) and 35.7% (5/14) for patients in the two groups, respectively (P=0.22). Bivariate analysis showed that prior exposure to fluoroquinolones (P=0.01) and antipseudomonal penicillins (P=0.004) as well as a higher number of antibiotics in use on the day of bacteraemia (P=0.02) were associated with isolation of a Co(S)/Ca(R) strain among patients with A. baumannii bacteraemia. Multivariate analysis using a backward logistic regression model showed that only exposure to fluoroquinolones was associated with development of Co(S)/Ca(R)A. baumannii bacteraemia (odds ratio=11.6; 95% confidence interval 2.4-55.9; P=0.02). The appearance of Co(S)/Ca(R)A. baumannii infections represents a major threat to critically ill hospitalised patients. Exposure to fluoroquinolones is an independent risk factor for development of Co(S)/Ca(R)A. baumannii bacteraemia.     

Primary antibiotic resistance in Helicobacter pylori strains isolated in northern and central Italy

BACKGROUND: Helicobacter pylori resistance to antibiotics is increasing worldwide, and it reduces the efficacy of therapy. AIM: To assess current primary antibiotic resistance in H. pylori strains isolated in Italy. METHODS: Between June 2004 and June 2006, H. pylori strains were isolated consecutively in the two participating centres (Bologna, northern Italy; Rome, central Italy) from patients never previously treated for the infection. Isolated strains were tested for primary clarithromycin, metronidazole and levofloxacin resistance using as break point the minimal inhibitory concentration >/=1, >/=8 and >/=1 mg/L for the three antibiotics, respectively. RESULTS: Overall, 255 H. pylori strains were evaluated. The resistance rate was 16.9% for clarithromycin, 29.4% for metronidazole and 19.1% for levofloxacin. Clarithromycin resistance was significantly higher in non-ulcer dyspepsia than in peptic ulcer patients (19.1% vs. 0%, P = 0.02), metronidazole resistance was higher in foreign than Italian patients (50% vs. 22.9%, P = 0.0004) and levofloxacin resistance was higher in old than younger patients (28.4% vs. 14.4%, P = 0.048). Levofloxacin resistance was also more frequent in those strains with either clarithromycin or metronidazole resistance. CONCLUSION: A very high rate of primary resistance towards the tested antibiotics was detected in our study.     

Retrospective Evaluation of Therapies for Staphylococcus aureus Endocarditis

We retrospectively evaluated antiinfective therapy for methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) endocarditis in 54 patients who had 57 treatment courses for the disease. Three treatments were assessed: 27 nafcillin-treated courses of MSSA endocarditis, 18 vancomycin-treated courses of MSSA endocarditis, and 11 vancomycin-treated courses of MRSA endocarditis. At baseline, patients with MSSA treated with vancomycin had more chronic conditions (p<0.01), a lower frequency of intravenous drug use (p<0.01), a lower hematocrit concentration (p<0.05), and a higher serum creatinine concentration (p<0.05) than the nafcillin group. Vancomycin-treated patients had a higher complication rate during therapy (p<0.05) and a longer duration in an intensive care unit (p<0.01) than the nafcillin group. The trend was for a higher complete response rate in the nafcillin group (74% vs 50%, p=0.12), but no difference in mortality (22% vs 28%, p=0.73). Patients with MRSA infection treated with vancomycin had higher mortality than those with MSSA who received that drug (55% vs 28%, p=0.24). Patients with vancomycin-treated MSSA endocarditis may have a poorer outcome than those who receive nafcillin, but this may be influenced by different or more severe clinical features. (Pharmacotherapy 1997;17(5):990–997)